4-Fluoroaniline → HCID 58949712, compound

HRID 1641299Notes

Reaction equation

HRID 1641299 reaction equation
[CH2:1]([N:8]1[CH2:26][CH2:25][C:11]2([N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[C:14](=[O:23])[CH2:13][C:12]2=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:39][C:40]1[CH:46]=[CH:45][C:43]([NH2:44])=[CH:42][CH:41]=1>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:26][CH2:25][C:11]2([N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[C:14](=[O:23])[CH:13]=[C:12]2[NH:44][C:43]2[CH:45]=[CH:46][C:40]([F:39])=[CH:41][CH:42]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 59252699HCID 59252699, compound

Product 1

HCID 58949712HCID 58949712, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 55 mg (0.156 mmol) 8-benzyl-1-(3-fluorophenyl)-1,8-diazaspiro[4.5]decane-2,4-dione in 2 mL dry toluene was added 36 mg (0.187 mmol)p-toluenesulfonic acid monohydrate and 0.030 mL (0.312 mmol) 4-fluoroaniline. The reaction mixture was refluxed for 24 hrs. The solvent was then removed by concentration in vacuum. The residue was purified by preparative HPLC (5→95% CH3CN/H2O over 30 min, 0.05% added TFA, C18 PRO YMC 20×150 mm) to afford 8-benzyl-1-(3-fluorophenyl)-4-[(4-fluorophenyl)amino]-1,8-diazaspiro[4.5]dec-3-en-2-one as a white solid. 1H NMR (CD3OD, 400 MHz): δ 7.50-7.20 (m, 7H), 7.20-6.98 (m 6H), 5.24 (s, 1H), 3.60 (s, 2H), 2.99-2.80 (m, 2H), 2.36-2.43 (m, 2H), 2.24-1.98 (m, 2H), 2.10 (m, 1H), 1.00 (m, 2H). High resolution mass spec (FT/ICR): calc M+H=446.2039 found 446.2035.

Workup

  1. temperatureThe reaction mixture was refluxed for 24 hrs
  2. customThe solvent was then removed by concentration in vacuum
  3. customThe residue was purified by preparative HPLC (5→95% CH3CN/H2O over 30 min
  4. addition0.05% added TFA

Sources & evidence

ORD record
ord-2c99f1bc68ad4ca98cd34a09a1cd2c2c
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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